Alcohols and amines are ubiquitous in the synthesis of agrochemicals, pharmaceuticals (e.g. protection, deprotection), flavors, fragrances, and advanced materials. (A. Ricci, Modern Amination Methods, Wiley, New York, 2000; Modern reduction methods, (Eds.: P. G. Andersson, I. J. Munslow) Wiley, New York, 2008; J. S. Carey, D. Laffan, C. Thomson, M. T. Williams, Org. Biomol. Chem. 2006, 4, 2337.)
One approach to access these compounds is via the reduction of amides. Amides are however, the most stable carboxylic acid derivative. (C. M. Breneman, M. Martinov in The Amide Linkage Structural Significance in Chemistry, Biochemistry, and Materials Science (Eds.: A. Greenberg, C. M. Breneman, J. F. Liebman), John Wiley and Sons Ins., New Jersey, 2003, p. 1-33; M. B. Robin, F. A. Bovey, H. Basch in The Chemistry of Amides (Ed.: J. Zabicky), Interscience, New York, 1970, p. 1-72.) Consequently, the reduction of amides typically requires stoichiometric amounts of active Al—H, B—H, or Si—H reducing agents that often cause reductive cleavage of the C═O bond (J. Seyden-Penne, Reductions by the Alumino and Borohydrides in Organic Synthesis, 2nd Ed., Wiley-VCH, New York, 1997. G. W. Gribble, Chem. Soc. Rev. 1998, 27, 395; G. Pelletier, W. S. Bechara, A. B. Charette, J. Am. Chem. Soc. 2010, 132, 12817; S. Das, D. Addis, S. Thou, K. Junge, M. Beller, J. Am. Chem. Soc. 2010, 132, 1770; Y. Sunada, H. Kawakami, T. Imaoka, Y. Matoyama, H. Nagashima. Angew. Chem. Int. Ed. 2009, 48, 9511, C. Cheng, M. Brookhart, J. Am. Chem. Soc. 2012, DOI: 10.1021/ja304547s)
Numerous heterogeneous catalysts have been developed to hydrogenate amides. These include copper-chromite systems that give mixtures of amine products under 350 atm H2, 250-400° C. (B. Wojcik, H. Adkins, J. Am. Chem. Soc. 1934, 56, 2419; R. M. King, U.S. Pat. No. 4,448,998, May 15, 1984.) Co-catalysts of Rh or Ru with Re, W, or Mo hydrogenate amides either via reductive cleavage of the C═O bond (100 atm H2, 160-180° C.), (C. Hirosawa, N. Wakasa, T. Fuchikami, Tetrahedron Lett. 1996, 37, 6749) or with selectivity for hydrogenating primary amides to the corresponding primary amines (20-100 atm H2, 130-160° C.). (G. Beamson, A. J. Papworth, C. Philipps, A. M. Smith, R. J. Whyman, J. Catal. 2011, 278, 228; Adv. Synth. Catal. 2010, 352, 869; J. Catal. 2010, 296, 93.)
There are a handful of homogeneous systems that catalyze the hydrogenation of amides or amide derivatives. The first is a Ru-triphos system (triphos=1,1,1-tris(diphenyl-phosphinomethyl)ethane) that hydrogenates primary amides with a preference for reductive cleavage of the C═O bond in the presence of NH3 (40 atm H2, 140-164° C., 14 h). (M. Kilner, D. V. Tyers, S. P. Crabtree, M. A. Wood, PCT Int. Pat. Appl. WO 03/093208 A1, Nov. 13, 2003; A. A. N. Magro, G. R. Eastham, D. Cole-Hamilton, Chem. Commun. 2007, 3154; US Pat. 2010/0010261 A1, Jan. 14, 2010.)
Beginning in 2006, Ikariya et al. reported dihydrogenations of cyclic imides, (M. Ito, A. Sakaguchi, C. Kobayashi, T. Ikariya, J. Am. Chem. Soc. 2007, 129, 290; M. Ito, C. Kobayashi, A. Himizu, T. Ikariya, J. Am. Chem. Soc. 2010, 132, 11414) N-acyl carbamates, N-sulfonyl-lactams, N-acylsulfonamides, (M. Ito, L. W. Koo, A. Himizu, C. Kobayashi, A. Sakaguchi, T. Ikariya. Angew. Chem. Int. Ed. 2009, 48, 1324) N-phenyl lactams and benzamides (T. Ikariya, M. Ito, T. Ootsuka, PCT Int. Pat. Appl. WO 2010/073974 A1, Jul. 1, 2010; M. Ito, T. Ootsuka, R. Watari, A. Shiibashi, A. Himizu, T. Ikariya, J. Am. Chem. Soc. 2011, 133, 4240.) with reductive cleavage of the C—N bond catalyzed by [Cp*RuCl(PN)] [Cp*=η5-C5(CH3)5; e.g. PN═Ph2P(CH2)2NH2] or [Cp*RuCl(LN)] e.g. (LN=2-C5H4NCH2NH2) (tBuOH or 2-PrOH, 80-100° C., 30-50 atm, KOtBu 1-2.5 equiv, 2-72 h).
Recently reported is the enantioselective monohydrogenation of meso-cyclic imides to give hydroxy lactams with trans-[Ru(H)2(BINAP)(dpen)] (BINAP=2,2′-bis(diphenyl-phosphino)-1,1′-binaphthyl) and dpen=1,2-diphenylethylenediamine) and related complexes in THF at low temperatures (0.1 mol % Ru, 0° C., 50 atm H2, 9 mol % tBuOK, 17-57 h). (S. Takebayashi, J. M. John, S. H. Bergens, J. Am. Chem. Soc. 2010, 132, 12832; S. Takebayashi, S. H. Bergens, PCT Int. Pat. Appl. WO 2010/145024 A1, Jun. 17, 2010.) Catalysts such as trans-[Ru(H)2(BINAP)(dpen)] have been shown to be active towards amide hydrogenation, however they can decompose at the higher temperature required for this transformation.
The most active system to date is Milstein's dearomatized, bipyridyl-based PNN Ru complex (PNN=(2-(di-tert-butylphosphinomethyl)-6-(diethylaminomethyl)pyridine) that hydrogenates a variety of secondary amides, and tertiary amides with ether groups to give the alcohol and amine products with 1 mol % Ru in THF (base free, 110° C., 10 atm H2, 48 h). (E. Balaraman, B. Gnanaprakasam, L. J. W. Shimon, D. Milstein, J. Am. Chem. Soc. 2010, 132, 16756.)
Recently reported is the low-T preparation and study of the Noyori ketone hydrogenation catalyst trans-[Ru((R)-BINAP)(H)2((R,R)-dpen)] (1). (R. J. Hamilton, C. G. Leong, G. Bigam, M. Miskolzie, S. H. Bergens, J. Am. Chem. Soc. 2005, 127, 4152; R. J. Hamilton, S. H. Bergens, J. Am. Chem. Soc. 2006, 128, 13700; J. Am. Chem. Soc. 2008, 130, 11979.)

Compound (1) is remarkably active towards carbonyl reduction. For example, (1) adds acetophenone on mixing and adds gamma-butyrolactone within minutes at −80° C. to form the alkoxide, trans-[Ru((R)-BINAP)(H)(OCH(CH3)(Ph))((R,R)-dpen)] and the corresponding Ru-hemiacetaloxide of gamma-butyrolactone. (1) Also catalyzes the hydrogenation of ethyl hexanoate under 4 atm H2 below 0° C. (S. Takebayashi, S. H. Bergens, Organometallics. 2009, 28, 2349.) and the monohydrogenation of meso-cyclic imides at 0° C. (S. Takebayashi, J. M. John, S. H. Bergens, J. Am. Chem. Soc. 2010, 132, 12832; S. Takebayashi, S. H. Bergens, PCT Int. Pat. Appl. WO 2010/145024 A1, Jun. 17, 2010.) However, compound (1) has not be used in amide hydrogenation reactions.
It is, therefore, desirable to provide processes and catalysts for the hydrogenation of amides.
This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention.